桂枝新加汤对颈椎间盘退变大鼠模型椎间盘TNF-α及血清中炎症因子的影响  

Effect of Guizhi Xinjia Decoction(桂枝新加汤)on TNF-αin Intervertebral Discs and Inflammatory Factors in Serum of Rat Model of Cervical Disc Degeneration

作　　者：李兆勇 杨雷 郭彦涛[1] 陈龙 李硕夫[1] 贺美宇 张超[1] 杨少锋[1] LI Zhaoyong;YANG Lei;GUO Yantao;CHEN Long;LI Shuofu;HE Meiyu;ZHANG Chao;YANG Shaofeng(The First Hospital of Hunan University of Chinese Medicine,Changsha 410007,Hunan,China;Hunan University of Chinese Medicine,Changsha 410007,Hunan,China)

机构地区：[1]湖南中医药大学第一附属医院,湖南长沙410007 [2]湖南中医药大学,湖南长沙410007

出　　处：《辽宁中医杂志》2024年第12期184-188,I0018,I0019,共7页Liaoning Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(8174402);湖南省自然科学基金青年基金项目(2023JJ40504,2020JJ5443);长沙市自然科学基金项目(kq2208203);湖南省教育厅计划项目(21C0233);湖南省卫生健康委员会计划项目(202204074858);湖南省中医药科研计划项目(B2023029);湖南中医药大学校级科研项目(2022XYLH007);湖南中医药大学国家自然科学基金项目预研项目(2024XJYY13)。

摘　　要：目的依据前期桂枝新加汤治疗颈椎病网络药理学研究结果,在动物实验中对桂枝新加汤治疗颈椎病的作用机制进行初步验证。方法前期网络药理学筛选出桂枝新加汤治疗颈椎病有关的磷脂酰肌醇4,5-二磷酸3-激酶催化亚基α(phosphatidylinositol 4,5-diphosphate 3-kinase catalytic subunitα,PIK3CA)、信号转导和转录激活因子3(signal transduction and transcription activator 3,STAT3)、肿瘤蛋白P53(tumor protein P53,TP53)、白细胞介素-6(interleukin-6,IL-6)、肿瘤坏死因子(tumor necrosis factor,TNF)、丝裂原激活蛋白激酶14(mitogen activated protein kinase 14,MAPK14)等主要作用靶点,涉及MAPK、磷脂酰肌醇3激酶(phosphatidylinositol 3 kinase,PI3K)-蛋白激酶B(protein kinase B,AKT)等多条与炎症调节相关通路。在动物实验中,采用动静力失衡法构建颈椎间盘退变大鼠模型,观察桂枝新加汤对模型大鼠疼痛阈值、椎间盘组织HE染色、椎间盘内TNF-α及外周血清TNF-α、P物质(substance P,SP)、前列腺素E_(2)(prostaglandin E_(2),PGE_(2))等炎症因子的影响,初步验证桂枝新加汤治疗颈椎病的作用机制。结果与模型组比较,桂枝新加汤干预颈椎间盘退变大鼠模型2、4、8周,降低外周血清PGE_(2)、SP、TNF-α含量(P<0.01);桂枝新加汤干预8周,能有效的降低颈椎间盘TNF-α水平(P<0.05)。结论桂枝新加汤能提高机械刺激疼痛阈值,降低颈椎间盘退变大鼠血清中SP、PGE_(2)、TNF-α及颈椎间盘内TNF-α表达,起到缓解颈椎病疼痛的作用,成功验证了网络药理学部分结果。Objective To preliminarily verify the mechanism of Guizhi Xinjia Decoction(桂枝新加汤,GZXJD)in the treatment of cervical spondylosis in animal experiments based on the results of previous network pharmacology research on the treatment of cervical spondylosis.Methods The main targets of phosphatidylinositol 4,5-diphosphate 3-kinase catalytic subunitα(PIK3CA),signal transduction and transcription activator 3(STAT3),tumor protein P53(TP53),interleukin-6(IL-6),tumor necrosis factor(TNF),mitogen activated protein kinase 14(MAPK14)and so on related to the treatment of cervical spondylosis by GZXJD were screened by network pharmacology in the previous stage,involving multiple pathways related to inflammation regulation such as MAPK and phosphatidylinositol 3 kinase(PI3K)-protein kinase B(AKT).In animal experiments,a rat model of cervical intervertebral disc degeneration was established by dynamic and static imbalance method.The effects of GZXJD on mechanical withdrawal threshold(MWT),HE staining of intervertebral disc tissue,the levels of TNF-αin intervertebral disc and peripheral serum of TNF-α,substance P(SP),prostaglandin E_(2)(PGE_(2))and other inflammatory factors of the model rats were observed.It preliminarily verified the mechanism of GZXJD in the treatment of cervical spondylosis.Results Compared with the model group,the intervention of GZXJD in the rat model of cervical intervertebral disc degeneration for 2,4 and 8 weeks reduced the levels of peripheral serum PGE_(2),SP and TNF-α(P<0.01).After 8 weeks,the level of TNF-αin cervical intervertebral disc can be effectively reduced(P<0.05).Conclusion GZXJD can increase the pain threshold of mechanical stimulation,reduce the levels of SP,PGE_(2) and TNF-αin serum and TNF-αin cervical disc in cervical disc degeneration rats,and play a role in relieving cervical spondylosis pain.The results of the network pharmacology part were successfully validated.

关 键 词：桂枝新加汤 颈椎病 网络药理学 疼痛 炎症因子 

分 类 号：R285[医药卫生—中药学]